This project will introduce a completely new approach for inducing mild hypothermia and cerebral cooling. Therapeutic Hypothermia (TH) has previously been shown to improve patient survival and neurological outcomes, but it has only been adopted by a small fraction of medical healthcare systems. The lack of adoption has, in part, been due to poor implementation methods that are either impractical, ineffective, or they interfere with EMS resuscitation efforts. This project will test and demonstrate a novel trans-nasal evaporative cooling device that solves these issues, which will facilitate a broader level of adoption and use of the therapy. Current induction techniques rely on some form of active cooling, whether by ice packs, cold saline or evaporative fluids. Our approach is novel in that we are harnessing a physiologic process that triggers the body to cool itself. There are no active cooling systems or evaporative chemicals. Our cooling method uses only dry, ambient air. The upper respiratory tract is very efficient at conditioning inspired air (prior to arrival at the luns), i.e., it can humidify dry air to full saturation very quickly. This humidifying process requires energy to convert water in the body to a vapor that is then mixed with the incoming dry air. Our cooling approach uses this physiological response to achieve the desired hypothermia. We force dry air through the nasal track and then extract the moisturized air, which effectively pulls energy and heat out of the body. This project will be completed in several sequential stages. In Phase I, we will build on our preliminary studies with pigs to optimize the cooling process variables, looking at a range of air flows and temperature. We will also develop a simple prototype device to deliver the therapy and to confirm the safety of the method. In Phase II, we will develop a clinical-grade device and perform additional pig studies to confirm that the induced hypothermia is safe, effective and is associated with improved outcome of resuscitation and short term neurologic function. We will end Phase II with a small human study to evaluate the safety, tolerability and efficacy of the process in humans. This work will validate a new method for inducing hypothermia that can be easily deployed during treatment of out-of-hospital cardiac arrest, as well as other ischemic injuries to the brain and the heart. We plan to continue our development program into larger clinical trials (post Phase II) to assess clinical benefits associated with introducing this therapy early after ROSC. Ultimately, we plan to leverage this grant program into the creation of a new product and therapy model that will have significant clinical and economic value.